Pituitary carcinoma in an Airedale terrier

Abstract

A 6-year-old Airdale terrier showed behavioral changes for 1 mo, progressing to neurological signs that included proprioceptive deficits, circling, anisocoria, and head pressing. A large, invasive, pituitary carcinoma was diagnosed at postmortem.

A 6-year-old, castrated male, Airedale terrier was examined numerous times by the referring veterinarian over a period of 1 mo. The initial complaint (day 1) was lethargy and reluctance to play or go for walks. No abnormalities were noted on physical examination, and the dog appeared bright and strong. Blood was drawn for a complete blood cell (CBC) count, biochemical profile, and thyroid panel. The serum appeared grossly lipemic and the biochemical profile revealed moderate increases in cholesterol and triglycerides and mild increases in serum alanine aminotransferase (ALT) and calcium. The concentration of thyroid stimulating hormone (TSH) was slightly elevated, and that of T4 was normal.

The dog's diet was changed to a low fat food (Waltham's Low Fat Canine; Waltham Veterinary Diets, Toronto, Ontario), and treatment with levothyroxine (Soloxine; Daniels Pharmaceuticals, St. Petersburg, Florida, USA) was initiated to rule out hypothyroidism. On day 7, the dog began urinating and defecating in the house. The inappropriate elimination was thought to be behavioral in origin; results of urinalysis, abdominal radiography, and neurological examination were normal. Over the next 2 wk, the dog became more lethargic and continued to void in the house. On re-examination by the referring veterinarian on day 21, neurological disease became the primary differential, as the dog scuffed the toenails of his left hind limb when circled to the right. It was also hypothesized that central nervous system (CNS) disease might also account for the progressive behavioral abnormalities. The owners declined referral to a neurologist.

On day 31, the dog showed signs of mental dullness, anorexia, pacing, circling to the right, and head pressing, and had vomited the previous evening. On examination by the referring veterinarian, the dog was mildly febrile (39.3°C; reference range, 37.5°C to 39°C), had a mydriatic left pupil and miotic right pupil, and dragged both hind limbs when walking. The dog was treated with IV 0.9% NaCl (MTC Pharmaceuticals, Cambridge, Ontario), 2 mL/kg BW/h; proparacaine penicillin (PenG; Citadel Animal Health, Cambridge, Ontario), 30 000 IU/kg BW, IM; and dexamethazone (Dexamethazone 2; Vetoquinol, Lavaltrie, Quebec), 0.6 mg/kg BW, IM. Two days later, on day 33, the dog was referred to the Veterinary Teaching Hospital at the University of Guelph.

Neurological evaluation revealed mental depression and lethargy. Enophthalmos of both eyes was evident, and the right eye deviated ventromedially. The left pupil was mydriatic and the right pupil was miotic. Both eyes were poorly responsive to light; however, menace responses were preserved. Examination of gait and posture showed compulsive circling to the right and proprioceptive deficits of the right forelimb and hind limb without obvious ataxia. Sensation of all limbs was intact, and patellar and withdrawal reflexes were normal.

A cerebrospinal fluid sample had a nucleated cell count of 0.001 × 10 9 /L (normal, < 0.003 × 10 9 /L); however, its protein content was increased substantially at 0.56 g/L (normal, < 0.25 g/L). These findings were suggestive of a nonsuppurative inflammatory process, with neoplasia being most likely.

Gross postmortem abnormalities included macro- and micronodularity of the pancreas, and pale, wet kidneys. In addition, an irregular, firm tan mass, 1.5 cm in diameter, was found in the pituitary fossa. It was adherent to the floor of the cranium and appeared to be disrupting the pituitary fossa and the optic nerves. No metastases were found, and the adrenal and thyroid glands appeared normal.

Histological examination of the pituitary tumor revealed a solid mass with an area of hemorrhage and necrosis. Encapsulation was not evident and the cells did not resemble normal pituitary tissue. Most cells were epithelial in nature, and some appeared to be keratinizing. Cells were arranged in nests in some areas of the tumor, while in other sections, acini and tubular structures were the predominant architecture. The cells exhibited 2-fold anisokaryosis and numerous mitotic figures. The diencephalon overlying the pituitary showed evidence of compression and discrete invasion, while the periosteum of the sphenoid bone underlying the tumor also showed evidence of invasion ( Figure 1 ). A diagnosis of

pituitary carcinoma was made, on the basis of the degree of anaplasia and local invasiveness.

Figure 1. A section through the thalamus at the level of the posterior commissure in a 6-year-old, castrated male, Airedale terrier with clinical signs of depression, aggression, circling, head pressing, and proprioceptive deficits. Arrows outline the .

Histological examination of the pancreas revealed replacement of normal tissue in some areas by adipose tissue. Nodules of hyperplastic normal tissue were also evident. These findings were supportive of chronic pancreatic atrophy. In addition, there were multiple areas of fat necrosis, indicative of acute pancreatitis. Marked, diffuse, fine vacuolation was observed in the liver. Swelling of hepatocytes and mild cholestasis was also evident, consistent with steroid hepatopathy. The pathological diagnoses in this case were pituitary carcinoma, acute pancreatitis, chronic pancreatic atrophy, and steroid hepatopathy.

Pituitary carcinomas are rare in domestic animals but have been reported in older dogs and cows (1 ). In a study by Sarfaty et al (2 ), the mean age of onset of neurologic signs due to large pituitary tumors in dogs was 11.4 ± 1.0 y. In this case, the dog was only 6 y old. Pituitary carcinomas are usually endocrinologically inactive (1 ). Unfortunately, neither adrenal corticotrophic hormone nor resting cortisol levels were measured in this dog. Lethargy was the only clinical sign consistent with hyperadrenocorticism. The carcinoma was assumed to be nonfunctional, as other signs of hyperadrenocorticism (such as polyuria, polydipsia, polyphagia, weight gain, hair loss, and pendulous abdomen) were not noted (3 ). Therefore, the etiology of the steroid hepatopathy was probably iatrogenic, rather than as a consequence of increased levels of endogenous corticosteroids (4 ).

The hyperlipidemia noted by the referring veterinarian on the initial blood sample was not accompanied by increases in serum amylase or lipase, but it may have predisposed the dog to acute pancreatitis. However, no clinical signs of pancreatitis were noted until just prior to referral, when the dog was anorexic and vomiting. These signs may be attributed to pancreatitis; however, destruction of the dorsolateral portion of the hypothalamus by the invading tumor might also cause anorexia (5 ). Pancreatitis may have contributed to the severe depression noted a few days prior to presentation at the Veterinary Teaching Hospital, but the depression was more likely a result of the enlarging pituitary tumor (5 ,6 ). Pancreatitis may also have accounted for the mild anemia and neutrophilia with the left shift (7 ). Hepatic ischemia or exposure to pancreatic toxins could account for the increases in serum ALT and ALP (7 ). The elevation in serum bilirubin might also be attributed to hepatocellular damage; however, intra- or extrahepatic biliary obstruction could not be ruled out (7 ). The histological diagnosis of exocrine pancreatic insufficiency was unexpected in this case, as the dog showed no signs of chronic diarrhea, steatorrhea, weight loss, or increased appetite (8 ).

Destruction of the pars distalis and neurohypophysis by an invading pituitary carcinoma may result in panhypopituitarism and diabetes insipidus (1 ). These abnormalities did not occur in this case. Thyroid stimulating hormone levels measured by the referring veterinarian were mildly increased rather than decreased, as would occur with hypopituitarism. Additionally, urine specific gravity at the time of referral was high normal, which would rule out a deficiency of antidiuretic hormone production by the neurohypophysis.

Many of the clinical signs exhibited by this dog could be attributed to compression or invasion of the CNS by the pituitary tumor. Similar behavioral abnormalities, including lethargy, pacing, wandering, circling, and head pressing were observed in one study of dogs with very large pituitary tumors (2 ). Invasive or hemorrhagic lesions in the nuclei of the thalamic and hypothalamic reticular activating system may cause disturbances in consciousness, resulting in lethargy, disorientation, and semicoma (2 ). Circling may be attributable to tumor compression or invasion of the thalamus on the side toward which the dog circles (2 ,6 ). In this case, the dog circled to the right. In spite of the apparent disruption of the optic nerves, the intact menace responses showed that function of these nerves was preserved. Dilation of the left pupil was indicative of damage to the left oculomotor nerve, located in the midbrain directly caudal to the pituitary fossa (6 ). Suspected involvement of the midbrain was further substantiated by the ventromedial deviation of the right eyeball, as damage to the trochlear nerve, also located in the midbrain, results in medial strabismus of the ipsilateral eye (6 ). Proprioceptive deficits occurred in the right forelimb and hind limb without obvious ataxia. Proprioceptive deficits in the absence of ataxia indicate a lesion in, or rostral to, the midbrain (6 ). When the deficits are unilateral, as in this case, the lesion must be rostral to the midbrain on the contralateral side, owing to the crossover of white matter pathways that occurs at this location (6 ). Therefore, in this case, a lesion in, or rostral to, the midbrain on the left side was suspected. The dog's compulsive circling to the right supported the presence of a lesion in the right thalamocortex. The combination of cranial nerve deficits, circling, depression, and proprioceptive deficits in this dog suggested that the invasive and compressive nature of the pituitary carcinoma caused multiple, randomly distributed lesions that resulted in numerous CNS abnormalities.

Footnotes

Acknowledgments

The author thanks Dr. Gary Thompson for performing the postmortem and histological examinations, as well as for his input into the case report, Dr. Jeff Caswell for his advice and technical assistance, and Dr. Christine Winder, the referring veterinarian, for her time and effort in working up the case.

Dr. Puente will receive 50 free reprints of her article, courtesy of The Canadian Veterinary Journal. CVJ